Systemic administration of IL-12 greatly reduced the hepatic and lung metastases of intravenously injected liver and lung metastatic tumor cells in C57BL/6 +/+ and nu/nu mice. Cytotoxic assay in vitro revealed that administration of IL-12 greatly enhanced cytotoxicity of hepatic and pulmonary mononuclear cells (MNC) against various NK sensitive and resistant tumor targets, whereas only slight or moderate augmentation of the cytotoxicity was observed in splenocytes in normal and nude mice. Systemic administration of IL-12 into normal and nude mice markedly augments the NK1 expression of NK1^+TCR^<int> cells (NK1^<high>TCR^<int>). Depletion of either NK1.1^+ or CD3^+ cells, but not CD8^+ cells, of hepatic and pulmonary MNC from IL-12 treated normal mice by respective Abs and C in vitro abrogate their cytotoxicity. It was confirmed by the cytotoxic assay after cell sorting that NK1^<high>TCR^<int> cells had much stronger cytotoxicity than hepatic and pulmonary NK cells. These results neve
… Morealed that TCR^<int> cells are potent cytotoxic effector cells and suggest that NK1^<high>TCR^<int> cells are the main anti-metastatic population in the liver and lung, and that TCR^<int> cells are functionally different from regular T cells with bright TCR.Next, we report that cytotoxic CD3^+ CD56^+ cells are selectively expanded when monocyte depleted human PBL [M(-) PBL] were cultured with 20 U/ml IL-12 and 100 U/ml of IL-2, In a majority of cases, CD4^-8^- as well as CD8^+ gammadelta T cells with CD56 Ag were induced. In some cases, CD4^+CD56^+ alphabeta T cells were selectively expanded. Whether gammadelta T cell or ab T cells expand is dependent on inbividuals. When M(-) PBL were cultured by IL-2 alone, CD3^+ CD56^- cells predominantly expanded, while CD3^+ CD56^+ cells remained to be a minor population. Cytotoxic activity of M(-) PBL cultured with a combination of IL-12 and IL-2 is much greater than that of M(-) PBMC cultured with IL-2 alone. The cytotoxicity of M(-) PBL was abrogated by the depletion of either CD3^+ or CD56^+ cells irrespective of their gammadelta or alphabeta phenotypes. These types of cells preferentially present in the livers of humans. These results revealed that, in a certain condition, IL-12 synergizes with IL-2 to induce potent cytotoxic T cells with CD56 Ag of humans and suggest that these cells in the human liver are a similar functional population to NK1^+ alphabeta T cells in murine liver. Less